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Hyaluronan-Based Hydrogels as Functional Vectors for Standardised Therapeutics in Tissue Engineering and Regenerative Medicine
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Alexandre Porcello, Alexis Laurent, Nathalie Hirt-Burri, Philippe Abdel-Sayed, Anthony de Buys Roessingh, Wassim Raffoul, Olivier Jordan, Eric Allémann, Lee Ann Applegate
To avoid in vivo solubilisation and subsequent expedited clearance, hyaluronan properties may be improved through cross-linking processes (Segura et al. 2005). Varying degrees of cross-linking enable the formation of polymeric hydrogel networks, conferring a uniform behaviour to the material, which might be considered as a chemical and physical barrier against enzyme and free radical degradation (Tezel and Fredrickson 2008). Specifically, rates of enzymatic degradation mediated by hyaluronidases are related to the degree of cross-linking of hyaluronan hydrogels, wherein higher degrees of cross-linking are associated with relatively improved stability. Additionally, cross-linking degrees along with polymer concentration greatly influence hydration balance values of specific hydrogels, defining the parameters for environmental water uptake and absorption. As an illustration thereof, the hydration balance in dermal fillers is generally achieved with 5.5 mg HA/mL of water and a typical degree of 4% cross-linking. Considering relatively higher hyaluronan concentrations (i.e. 20–24 mg/mL), the hydration balance values generally lead to important absorption of environing water by the product (Tezel and Fredrickson 2008).
Introduction and Review of Biological Background
Published in Luke R. Bucci, Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Synovial fluid is produced by synoviocytes and consists mainly of a plasma filtrate with few or no proteins above 150,000 Da and a protein content (mostly albumin) of 1.5 to 2 g/dl. In addition to lubricin, a glycoprotein that helps lubricate joint surfaces, the major feature of synovial fluid is hyaluronate. Synovial fluid is viscous and slimy from an approximately 0.2% solution of hyaluronate, a long, nonsulfated glycosaminoglycan. Hyaluronate helps to reduce friction in joints, allowing easy movement of joints without excessive wear. The friction coefficient of synovial joints is 0.003 to 0.015, compared to 0.02 for an ice skate on ice, and 1 for automobile tires on the road. Synovial fluid is probably the major route for nutritional supply to cartilage and chondrocytes. As such, the gel-like properties of hyaluronate solutions influence the passage of large molecules and proteins. Small molecules and ions, such as oxygen, glucose, and calcium, are free to diffuse through the hyaluronate gel.
The effect of seprafilm on adhesions in strabismus surgery — an experimental study
Published in Jan-Tjeerd de Faber, 28th European Strabismological Association Meeting, 2020
Seyhan B. Özkan, Erkin Kır, Nil Culhacı, Volkan Dayanır
Seprafilm is an absorbable membrane composed of sodium hyaluronate and carboxymethylcellulose both of which are anionic polysaccharides. Hyaluronate is ubiquitously present in soft tissues, synovial fluid, umbilical cord and vitreous. Carboxymethylcellulose has widespread application in the pharmaceutical and chemical industries.
Low plasma hyaluronan is associated with faster functional decline in patients with amyotrophic lateral sclerosis
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
Cory J. Holdom, Shyuan T. Ngo, Pamela A. McCombe, Robert D. Henderson, Frederik J. Steyn
Hyaluronan was significantly correlated with ΔFRS, and so we investigated whether hyaluronan would be predictive for survival. Forty-two deaths were recorded during this study; there was no association between measures of plasma hyaluronan and disease duration (time since symptom onset to time of death; τ = 0.034, p = 0.773). A cox regression was performed with age, sex, hyaluronan, and ΔFRS as predictors, with an interaction term for hyaluronan and ΔFRS, and age and hyaluronan. Stepwise AIC selection was used to create the final model; sex and the age/hyaluronan terms were dropped. In the final model (Table 3), age had a hazard ratio (HR) of 1.048 (95% CI: [1.003, 1.095], p = 0.036), hyaluronan had a HR of 0.981 (95% CI: [0.963, 1.000], p = 0.056), ΔFRS had a HR of 0.251 (95% CI: [0.072, 0.870], p = 0.029), and the interaction term had a HR of 0.959 (95% CI: [0.935, 0.983], p < 0.001). Kaplan-Meier plots based on plasma hyaluronan (in quartiles) were constructed and the curves were compared using a log-rank test (Figure 3). As established, ΔFRS was strongly predictive for probability of survival (p < 0.001, Figure 3(A)). There was no difference in survival probability between the low hyaluronan and high hyaluronan groups (p = 0.537, Figure 3(B)).
Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug
Published in Expert Opinion on Investigational Drugs, 2020
Marwa Sabha, Bernadette C. Siaton, Marc C. Hochberg
There are some challenges for the use of lorecivivint in the management of symptomatic knee OA. Lorecivivint is a medication that is administered by intraarticular injection, this may limit the number of providers who will be able to administer it. Also, to verify that the drug is administered in the joint space, and to exclude the possibility of drug leak in cases of lack of efficacy, lorecivivint is administered under ultrasound guidance. This will be challenging and may limit the number of providers using it due to insufficient training and/or lack of ultrasound machine availability in some practices. Also, in the current trials, only one knee is being injected, however, half of the symptomatic patients with knee OA have bilateral knee involvement. We have no data about the safety and efficacy of bilateral injections, whether it can be given at the same visit or different visits, and the recommended duration between injections. Lastly, we know from clinical practice that intraarticular steroid injections usually are given every 3 months and intraarticular hyaluronate injections usually are given every 6 months. However, we have no information regarding the efficacy and safety of lorecivivint in multiple injections.
Potential mechanism of thymosin-α1-membrane interactions leading to pleiotropy: experimental evidence and hypotheses
Published in Expert Opinion on Biological Therapy, 2018
Walter Mandaliti, Ridvan Nepravishta, Francesca Pica, Paola Sinibaldi Vallebona, Enrico Garaci, Maurizio Paci
Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. Due to some similarity in the aminoacidic sequence between Tα1 and the sequences found to interact with HA the hypothesis that an interaction may occur was investigated [86]. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1. This suggests a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. The interaction is substantially electrostatic due to charged residues of both the interacting macromolecules and involves only a limited structuration effect in the conformation of Tα1 upon binding. Further studies are needed to confirm these observations since Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions may act to suppress both T-cell reactivity and tumor progression.